それにしても is a sentence-initial conjunction that means 'even so' or 'nevertheless.' It is used when you acknowledge what the other person said, but you want to point out something that seems contradictory or surprising in light of it. It often carries a tone of mild criticism, amazement, or disbelief.

For example, if someone tells you it rained all day, you might say それにしても寒すぎる (even so, it's too cold). It shows that you accept the premise but find the situation extreme. It can also be used to shift the topic slightly, as in 'anyway' or 'at any rate,' when you want to move on but still connect to the previous point.

This phrase is common in both speaking and writing. In speech, it is often used to express personal feelings, such as surprise or frustration. In writing, it can appear in essays or formal statements but is not overly literary. It is safe to use in most situations, but it is a bit more emphatic than just でも (but).